scholarly journals Ubiquitin Pathway Is Associated with Worsening Left Ventricle Function after Mitral Valve Repair: A Global Gene Expression Study

2020 ◽  
Vol 21 (14) ◽  
pp. 5073
Author(s):  
Feng-Chun Tsai ◽  
Gwo-Jyh Chang ◽  
Ying-Ju Lai ◽  
Shang-Hung Chang ◽  
Wei-Jan Chen ◽  
...  

The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and p70S6K signaling. In addition, worsening-LVF was associated with altered expressions of genes pathologically relevant to heart failure, such asdownregulated apelin receptors and upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). HL-1 cardiomyocyte cells transfected with ubiquitination-related genes demonstrated activation of the protein ubiquitination pathwaywith an increase in the ubiquitin activating enzyme E1 (UAE-E1). It also led to increased apoptosis, downregulated and ubiquitinated X-linked inhibitor of apoptosis protein (XIAP), and reduced cell viability. Overexpression of ubiquitination-related genes also resulted in degradation and increased ubiquitination of α-smooth muscle actin (SMA). In conclusion, worsening-LVF presented differential gene expression profiles from preserved-LVF after MV repair. Upregulation of protein ubiquitination-related genes associated with worsening-LVF after MV repair may exert adverse effects on LV through increased apoptosis and contractile protein degradation.

Author(s):  
Fadi Hage ◽  
Ali Hage ◽  
Stuart Smith ◽  
A. Dave Nagpal ◽  
Michael W. A. Chu

Both surgical and percutaneous mitral repair remain contraindicated in patients with severe degenerative mitral regurgitation (DMR) with severe left ventricular (LV) dysfunction because of inadequate LV reserve and increased LV work with a competent mitral valve. We report a 55-year-old gentleman who presented in cardiogenic shock with missed severe DMR and severe LV dysfunction, in whom we performed a high-risk mitral repair and insertion of a prophylactic CentriMag LV assist device. This innovative approach was found to be successful with significant patient improvement in both LV function and clinical symptoms with a competent mitral valve.


Heart ◽  
2017 ◽  
Vol 104 (10) ◽  
pp. 855-860 ◽  
Author(s):  
Emilie Vitel ◽  
Elena Galli ◽  
Christophe Leclercq ◽  
Maxime Fournet ◽  
Christian Bosseau ◽  
...  

ObjectiveTo assess if the lack of development of right ventricular (RV) contractile reserve during exercise echocardiography (ex-echo) might be a predictor of postoperative major adverse cardiovascular events (MACEs) in patients with primary mitral regurgitation (pMR) undergoing early surgery.MethodsComprehensive resting and ex-echo were performed in 142 asymptomatic patients (58±21 years, 68% men, New York Heart Association functional class ≤2) with isolated severe pMR and preserved left ventricular (LV) function (LV ejection >60%, LV end-systolic diameter <45 mm) undergoing mitral valve replacement (n=20) or repair. Postoperative MACEs were defined as occurrence of atrial fibrillation, stroke, cardiac-related hospitalisation or death. RV function was evaluated at rest in every patient during ex-echo by measuring their tricuspid annular plane systolic excursion (TAPSE) value.ResultsAfter median follow-up of 30 months (IQR 16–60 months), MACEs occurred in 48 (34%) patients. Using Bayesian model averaging, among all the characteristics including the type of surgery, exercise TAPSE (ex-TAPSE) emerged as the most likely predictor of prognosis (HR 0.91, 95% CI 0.86 to 0.96). Other probable predictors were exercise fractional area change (HR 0.02, 95% CI 0.00 to 0.80), male gender (HR 0.40, 95% CI 0.21 to 0.75) and RV basal diameter (HR 1.06, 95% CI 0.98 to 1.14). In the receiver operating characteristic curve analysis, an ex-TAPSE value of <26 mm (sensitivity 73% (95% CI 61 to 84) and specificity of 86% (95% CI 77% to 93%)) defined RV dysfunction. Event-free survival at 5 years was significantly lower in the patient group that exhibited no development of RV contractile reserve during exercise: 43.9% (95% CI 31.3 to 61.4) vs 75.8% (95% CI 64.8 to 88.7).ConclusionLack of development of exercise-induced RV contractile reserve is a prognostic predictor in patients with severe pMR undergoing early mitral valve surgery.


2019 ◽  
Vol 68 (06) ◽  
pp. 462-469 ◽  
Author(s):  
Daniel Grinberg ◽  
Matteo Pozzi ◽  
Marine Bordet ◽  
Kaled Adamou Nouhou ◽  
Young Joon Kwon ◽  
...  

Background In patients with secondary mitral regurgitation (MR) associated with low ejection fraction or previous heart surgery, minimally invasive mitral valve surgery without aortic cross-clamp (MIMVS-WAC) has shown promising results. We report our experience for this strategy in our centers. Methods Between August 2011 and April 2017, 46 patients (mean age 69 ± 11 years, 76% males) received MIMVS-WAC. Indications for this technique were prior coronary bypass surgery (26%), severe or recent left ventricular (LV) dysfunction (30%), or both (39%). The mean EuroSCORE II was 12 ± 10. Results For each procedure, we conducted right minithoracotomy and hypothermic cardiopulmonary bypass (CPB) after peripheral cannulation. Mean CPB time was 159 ± 39 minutes. A mitral valve replacement (MVR) was performed in 23 cases (50%), an annuloplasty in 22 cases (48%), and a prosthesis pannus removal in 1 case (2%). Mean hospital length of stay was 12 ± 5.4 days. We report no sternotomy conversions, six reoperations for bleeding, and three deaths at 30 days. Transfusion was requested in 62% (mean infusion 2 ± 2.4 packed red blood cells). The postoperative echocardiography showed an LV function preservation in 69% of cases and a reduction of pulmonary arterial pressure in 73% of cases. Four additional deaths occurred in the long-term follow-up (mean 637 ± 381 days, median 593 days). No mitral reoperation was required, with a MR ≤ 2 in 90% of patients. Conclusion In high-risk patients, the MIMVS-WAC is a safe technique. It avoids hard dissections while ensuring excellent preservation of cardiac function.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Benito Gonzalez ◽  
X Freixa ◽  
C Godino ◽  
M Taramasso ◽  
R Estevez-Loureiro ◽  
...  

Abstract Background Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction, functional mitral regurgitation grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results 93 patients (68.2±10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-months follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0–17.8 vs 2.7–13.5, p=0.002), sustained VT or ventricular fibrillation (0.9–2.5 vs 0.5–2.9, p=0.012) and ICD antitachycardia therapies (2.5–12.0 vs 0.9–5.0, p=0.033) were observed. Conclusion PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort. Proportion of patients who presented ven Funding Acknowledgement Type of funding source: None


Author(s):  
Ana Devesa ◽  
Rafael Hernández-Estefanía ◽  
José Tuñón ◽  
Álvaro Aceña

Abstract Background Takotsubo syndrome is a frequent entity; however, it has never been described after a mitral valve surgery. Case summary  We present the case of a 79-year-old woman, with background of atrial fibrillation and a left atrial appendage closure device, who was admitted for elective mitral valve replacement, because of asymptomatic severe primary mitral regurgitation. Biologic mitral valve was implanted without incidences, but in the postoperative, she developed cardiogenic shock. Electrocardiogram (ECG) showed inverted T waves in precordial leads and an echocardiography showed severe left ventricular (LV) dysfunction with mid to distal diffuse hypokinesis, and better contractility in basal segments. Troponin levels were mildly elevated. With the suspicion of a postoperative acute coronary syndrome, a coronary angiography was performed and showed no significant coronary lesions. The haemodynamic situation was compromised for the next 48 h, in which vasoactive support and intra-aortic balloon counterpulsation were implemented. After 48 h, the haemodynamic situation suddenly improved. The ECG was normalized, and a control echocardiogram showed partial recovery of the LV function with resolution of regional wall motion abnormalities. The patient could be discharged at 1 week. The clinical picture was interpreted as a stress cardiomyopathy after mitral valve surgery. Discussion  Takotsubo syndrome is a threatening condition; complications in acute phase could lead to a fatal outcome. Mitral valve surgery has to be considered as a trigger for this entity, after excluding coronary involvement, specially of left circumflex artery.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yi Zhang ◽  
Wei-feng Yan ◽  
Li Jiang ◽  
Meng-ting Shen ◽  
Yuan Li ◽  
...  

Abstract Background Functional mitral regurgitation (FMR) is one of the most common heart valve diseases in diabetes and may increase left ventricular (LV) preload and aggravate myocardial stiffness. This study aimed to investigate the aggravation of FMR on the deterioration of LV strain in type 2 diabetes mellitus (T2DM) patients and explore the independent indicators of LV peak strain (PS). Materials and methods In total, 157 T2DM patients (59 patients with and 98 without FMR) and 52 age- and sex-matched healthy control volunteers were included and underwent cardiac magnetic resonance examination. T2DM with FMR patients were divided into T2DM patients with mild (n = 21), moderate (n = 19) and severe (n = 19) regurgitation. LV function and global strain parameters were compared among groups. Multivariate analysis was used to identify the independent indicators of LV PS. Results The T2DM with FMR had lower LV strain parameters in radial, circumferential and longitudinal direction than both the normal and the T2DM without FMR (all P < 0.05). The mild had mainly decreased peak diastolic strain rate (PDSR) compared to the normal. The moderate had decreased peak systolic strain rate (PSSR) compared to the normal and PDSR compared to the mild and the normal. The severe FMR group had decreased PDSR and PSSR compared to the mild and the normal (all P < 0.05). Multiple linear regression showed that the regurgitation degree was independent associated with radial (β = − 0.272), circumferential (β = − 0.412) and longitudinal (β = − 0.347) PS; the months with diabetes was independently associated with radial (β = − 0.299) and longitudinal (β = − 0.347) PS in T2DM with FMR. Conclusion FMR may aggravate the deterioration of LV stiffness in T2DM patients, resulting in decline of LV strain and function. The regurgitation degree and months with diabetes were independently correlated with LV global PS in T2DM with FMR.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Yedidya ◽  
R.P Lustosa ◽  
F Fortuni ◽  
P Van Der Bijl ◽  
F Namazi ◽  
...  

Abstract Background Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging because LV ejection fraction (LVEF) reflects changes in LV volume without taking into account the direction of the blood flow. LV global longitudinal strain better reflects active LV myocardial deformation but does not incorporate afterload. LV myocardial work derived from pressure-strain loops integrates speckle tracking echocardiography with non-invasive blood pressure measurement. Purpose To evaluate LV myocardial work components to better characterize LV function in patients with SMR. Methods 378 patients (72% men, median age 68 [range 60 to 74 years]) with various grades of SMR were retrospectively analysed. LV myocardial constructive work, wasted work and work efficiency were measured with speckle tracking echocardiography. Results 145 patients had mild SMR, 130 moderate SMR and 103 severe SMR. Patients with severe SMR had larger LV volumes, lower LVEF and more impaired LV GLS (Table 1). While LV constructive work was more impaired in patients with severe SMR, wasted work was lower as compared to mild SMR (Table 1). Consequently, patients with severe SMR had better myocardial work efficiency than patients with mild MR. This could reflect, the regurgitant volume which is pumped into a low pressure chamber (the left atrium) resulting in less myocardial wasted work and preservation of myocardial efficiency. Conclusion In patients with severe SMR, LVEF, LV GLS and myocardial constructive work are more impaired when compared to mild SMR. However, myocardial wasted work is lower, resulting in higher better LV myocardial work efficiency. Funding Acknowledgement Type of funding source: None


1994 ◽  
Vol 2 (2) ◽  
pp. 90-94
Author(s):  
Masaharu Shigenobu ◽  
Shunji Sano

This study compares mitral valve repair and mitral valve replacement with chordal preservation for chronic mitral regurgitation due to myxomatous degeneration with special reference to left ventricular function. Twenty-six patients underwent complete preoperative and 2 years later postoperative echocardiography study. Thirteen patients underwent mitral valve replacement associated with preservation of chordae tendineae and papillary muscles, and 13 patients had mitral valve repair. There were no statistically significant differences between the 2 groups for clinical findings, hemodynamic profiles, or left ventricular function compared prior to surgery. After correcting mitral regurgitation, increase in cardiac index was significant for the repair group. Left ventricular end-diastolic volume decreased in both groups. Left ventricular end-systolic volume significantly decreased in the repair group, but remained unchanged in the replacement group. Both ejection fraction and mean left ventricular circumferential fiber shortening velocity (mVcf) decreased in the replacement group, but significantly increased in the repair group 2 years after surgery. These findings suggest valve replacement with chordal preservation shows less improvement in ventricular systolic function late after surgery compared with mitral valve repair.


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